**Abstract**

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost every organ of the body and presents with a great variety of clinical features. SLE effect on kidneys, mostly referred to as lupus nephritis, is of special interest for the rheumatologist and nephrologist for three reasons. First, lupus nephritis is one of the commonest types of organ involvement in this disorder, affecting as up to 45% of all patients with SLE. Second, it presents with a great variety of clinical and histopathological findings, and thus, therapy must be tailored accordingly. Third, it greatly affects the morbidity and mortality of SLE patients. Taking these facts into account, this chapter is centered on lupus nephritis from the perspective of the clinical nephrologist and renal pathologist. This chapter elaborates the diversity of clinical features of lupus nephritis, in relation to the different histopathological forms of the disease and the therapeutic options that are available to date, as well as the pathogenesis, natural history, and prognosis of patients with lupus nephritis.

**Keywords:** lupus nephritis, histopathology, prognosis, management, end-stage kidney disease (ESKD)

#### **1. Introduction**

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with high heterogeneity. The hallmark of SLE pathogenesis is the production of autoantibodies [1], which results from a combination of genetic, epigenetic, environmental, hormonal, and immunoregulatory factors [2]. The heterogeneity is expressed with different clinical phenotypes that range from which organs are inflicted to the way that disease is caused at a specific organ and can be attributed to different autoantibody profiles, genetic variants, and interferon levels [3]. For example, there are two different phenotypes in patients with neuropsychiatric lupus [4], while there is a spectrum of different phenotypes concerning joint involvement in SLE [5]. This wide heterogeneity has even prompted researchers to question if SLE is a single disease [6] and highlights the difficulty of defining SLE. As a result, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) have developed criteria

to classify patients' disease as SLE. According to the most recent edition of these criteria [7], all patients considered to be classified as SLE must have a positive antinuclear antibody test and must accumulate certain clinical and immunological criteria.

Kidney involvement in SLE is a common and potentially life-threatening form of the disease. There are diverse ways with which SLE can cause kidney disease, such as lupus podocytopathy [8], tubulointerstitial disease [9], and syndromes like thrombotic thrombocytopenic purpura [10], but the usual form of kidney involvement is lupus nephritis (LN). LN is a form of glomerulonephritis in patients with SLE [8], which is characterized by the presence of stains for immunoglobulin G (IgG), immunoglobulin M (IgM), C3, and C1q in the immunofluorescence (IF) [11]. Patients with LN have been shown to have higher rates of morbidity and mortality compared with patients without renal involvement. There are different classes of LN that present with different clinical signs and have different prognosis [8].
